FDA’s Decision to Approve New Treatment for Alzheimer’s Disease

As gene-editing moves mainstream, a pioneer in the field is testing whether it could prevent Alzheimer's

David Liu is best known as one of the pioneers of the experimental science of editing people's genes.

Liu's laboratory at the Broad Institute of MIT and Harvard was the birthplace of two new types of gene-editing called base and prime editing, that swap out segments of the DNA strand without cutting into it. He and other experts estimate could be more precise and have less unintended effects than other forms of gene-editing like CRISPR. 

What's less known is that for the last five years, his laboratory has been quietly testing a method of potentially protecting people against one of the most devastating health conditions worldwide: Alzheimer's disease. 

One of the lab's first tests of this science is to see if it can be used to install a gene called APOE2 that is believed to significantly reduce the risk of a person getting Alzheimer's. The work is still in the very early stages, Liu told Insider. His team has published multiple papers indicating that they can make these changes in cell samples and is currently running additional experiments on mice.  

The concept of preventing Alzheimer's is gaining traction, with I-Mab Biopharma launching an early-stage trial earlier this week of a nasal vaccine for the disease. Biotechs Nuravax and Vaxxinity are also working on Alzheimer's vaccines. 

The benefits of gene-editing is that it could be a one-and-done drug. But it's still highly experimental, and is only being tested in humans with rare diseases right now. There's still many questions to be answered before tweaking the DNA of the 33 million people worldwide with Alzheimer's disease, let alone giving a new type of medication to people who are otherwise healthy but at risk of Alzheimer's disease in the future. 

Liu's Alzheimer's work is not only a significant test of new science — it could also help determine if and how gene-editing goes mainstream. 

Liu's work focuses on a gene that makes people up to 99.6% less likely to get Alzheimer's

No one knows exactly what causes Alzheimer's disease. At this point, there are a myriad of theories because there's not many biological characteristics that are found in every person with the disease. Most drug companies have focused on a protein called amyloid beta that builds up in the brain of some Alzheimer's patients, but not all patients have that buildup. 

There is a genetic mutation that has strong links to the disease: the APOE4 gene. But that, too, isn't definitive — just because you have the mutation doesn't mean you will get Alzheimer's disease.

However, there may be another way to stop the disease.

Research has shown that people with a similar gene, APOE2, are between 66% and 99.6% less likely to develop Alzheimer's disease. 

Liu and his research team zeroed in on this gene as they were developing the first base editing technology between 2013 and 2015. It was a somewhat arbitrary idea initially, Liu said, but checked all of the boxes: There was strong science linking APOE2 to Alzheimer's disease and promising signs that base editing could tweak that gene. 

The idea is to develop a treatment that would flip the baseline letters of the DNA strand — G, A, T and C — to turn APOE4 or another type of gene known as APOE3 into APOE2.

The lab is still running tests to answer key questions like how and where in the body to deliver the treatment, according to Liu.

Experts still wonder if gene therapies are too risky for the general population

Gladstone Institutes Associate Investigator Yadong Huang, who has studied APOE4 since 1985, thinks that Liu's idea of using gene-editing is the right strategy. It's clear that APOE2 protects against developing Alzheimer's disease, and Huang likes that the Liu lab's approach doesn't involve cutting the DNA strand, as scientists theorized that cutting the strand could cause problems. 

It does raise many questions, though. Who should get it: everyone, or only people with the high-risk APOE4 gene, asked neurologist-turned-venture-capitalist Doug Cole. And when would they need to get the gene therapy? 

Liu and his research team haven't answered those questions yet. But Liu pointed to another startup he co-founded, Beam Therapeutics, which is working with Verve Therapeutics on a gene therapy that could potentially cure heart disease. They're starting with patients who have a high risk of heart disease

 due to a genetic mutation, and stand to benefit the most from treatment.

"All of these therapeutics boil down to how to best balance potential benefit to the patient, to the potential risk to the patient," Liu said. "We have a whole plethora of next-generation CRISPR and non-CRISPR gene-editing technologies that offer new capabilities and could potentially be much more broadly applicable."